Cure and Curse: E. coli Heat-Stable Enterotoxin and Its Receptor Guanylyl Cyclase C

Philipp R Weiglmeier,Hanna Berkner,Paul Rösch

doi:10.3390/toxins2092213

Abstract

Enterotoxigenic Escherichia coli (ETEC) associated diarrhea is responsible for roughly half a million deaths per year, the majority taking place in developing countries. The main agent responsible for these diseases is the bacterial heat-stable enterotoxin STa. STa is secreted by ETEC and after secretion binds to the intestinal receptor guanylyl cyclase C (GC-C), thus triggering a signaling cascade that eventually leads to the release of electrolytes and water in the intestine. Additionally, GC-C is a specific marker for colorectal carcinoma and STa is suggested to have an inhibitory effect on intestinal carcinogenesis. To understand the conformational events involved in ligand binding to GC-C and to devise therapeutic strategies to treat both diarrheal diseases and colorectal cancer, it is paramount to obtain structural information on the receptor ligand system. Here we summarize the currently available structural data and report on physiological consequences of STa binding to GC-C in intestinal epithelia and colorectal carcinoma cells.

Highlights

Enterotoxigenic Escherichia coli (ETEC) are a major cause for acute secretory diarrhea in developing countries with insufficient sanitation and no adequate supply of clean water
ETEC associated diarrhea is virtually indistinguishable from cholera [3]
Heat-stable enterotoxins are small peptides that are secreted by enterotoxigenic bacteria

Summary

Introduction

Enterotoxigenic Escherichia coli (ETEC) are a major cause for acute secretory diarrhea in developing countries with insufficient sanitation and no adequate supply of clean water. These pathogens account for around a half million deaths per year, mostly of children in developing countries [1], and are the cause of traveller’s diarrhea. Heat-stable enterotoxins are small peptides that are secreted by enterotoxigenic bacteria. Other notable enterotoxins produced by pathogenic E. coli include the enteroaggregative heat-stable toxin EAST1 [17,18] which is structurally similar to STa, and Shiga toxin Stx produced by shiga-toxigenic E. coli (STEC)[19]

Structure of ST Peptides

The Heat-Stable Enterotoxin Receptor

Regulation of Intestinal Fluid Secretion and STa-Induced Diarrhea

Involvement of GC-C in Colorectal Cancer

Outlook